An endoscope device for diagnosing a lesion within a living body has been widely known. For example, a fluorescent endoscope device has been in practical use wherein excitation lights are irradiated onto a tissue surface of a living body, a fluorescent material contained in the living tissue is excited, and fluorescence emitted from the living tissue is imaged so as to obtain a fluorescent image. Such a fluorescent endoscope device may be used for diagnosing a lesion in the living tissue based on information contained in an acquired image.
When excitation lights are irradiated onto the surface of a living tissue and auto-fluorescence from the surface of the living tissue is detected, it is known that the intensity emitted by normal tissue is different from the intensity emitted by lesion tissue. Analysis of the fluorescent intensity distribution obtained from the auto-fluorescent image of a living tissue containing a lesion tissue region enables segmentation of the lesion tissue region and the normal tissue region. The living tissue shows a layer structure in which collagen or elastin, each of which generates auto-fluorescence, is primarily contained in the sub-mucosal layer. When the structure of the tissue of a mucous membrane that is situated in the upper layer of the sub-mucosal layer changes due to a lesion, the auto-fluorescence of the collagen or elastin is greatly affected and is attenuated before it reaches the superficial portion of the mucous membrane. Consequently, detection of the fluorescent intensity in a wavelength range of 420 nm-600 nm, which region includes the main auto-fluorescent wavelengths of collagen or elastin, enables information to be acquired that may be used for identifying a lesion tissue region that has developed in the mucosal layer.
It also is known that porphyrin, which is an organic compound that exists naturally within a living body, tends to accumulate in a tumor. The porphyrin, when excited using excitation light in the visible wavelength range from blue to green in a manner similar to that of collagen or elastin, generates auto-fluorescence having a peak wavelength in the vicinity of 630 nm, so the detection of fluorescence within an extremely narrow band of wavelengths that includes 630 nm is indicative that a tumor has developed in the living tissue. It is further possible that the administration of a fluorescent drug from outside the body, such as 5ALA (5-aminolevulinic acid), results in the accumulation of porphyrin in a tumor. As described above, the detection of an auto-fluorescent spectrum from the living tissue enables the extraction of different information that is contained in each spectral range.
A method and a device for diagnosing the presence of a lesion in living tissue by utilizing auto-fluorescence of the living tissue is disclosed in, for example, U.S. Pat. No. 5,769,792. The fluorescent endoscope device disclosed in this patent enables a lesion tissue region to be clearly visualized by utilizing a fluorescent image in a spectral range where the auto-fluorescent intensity of the lesion tissue is substantially different from that of normal tissue, and by utilizing another spectral range where the intensity of auto-fluorescence in the lesion tissue is substantially equal to that of normal tissue, enabling clear identification of the lesion tissue from the surrounding normal tissue.
Further, a method for diagnosing the presence of a lesion in living tissue is known that utilizes a substance that has an affinity for lesion tissue that has developed in the living body. Initially, a fluorescent substance is administered from outside the body to a site where the existence of a lesion is suspected. After some time, the fluorescent substance selectively combines with the lesion tissue, and fluorescence from the fluorescent substance is then detected by irradiating excitation lights onto the site. Such a technique enables clear identification of a lesion tissue region that has developed in the living body. As the fluorescent substance, a fluorescent probe as disclosed in patent publications WO 2003/079015 and WO 2004/005917 may be used.
A fluorescent probe typically is composed of, on the molecular level, a portion that combines with a substance that specifically participates in a process that occurs where a lesion tissue, such as a tumor, appears and develops (hereinafter, such a substance will be referred to as a ‘target substance’, and a pigment for generating fluorescence. Pigments that generate fluorescence can be selected from various commercially available pigments. For example, in patent publication WO 2003/079015, a fluorescent probe is disclosed composed of pigments having excitation wavelength peak(s) and fluorescent wavelength peak(s) in the wavelength range of 600 nm-1200 nm. The fluorescent probe can be manufactured at very low cost, and the verification that such a fluorescent probe is safe to use with living body tissue has already begun.
Furthermore, in patent publication WO 2004/005917, a fluorescent probe is disclosed that generates little fluorescence before combining with a target substance but, after combining with a target substance, the chemical structure of the probe changes so that the probe then generates a substantial fluorescence. Since the fluorescent probe generates a substantial fluorescence only when combined with a target substance, the accuracy of detecting a lesion can be improved by utilizing such a fluorescent probe. In addition, the fluorescent probe can be designed to selectively combine with only a specific target substance so that the selection of a target substance that has characteristics unique to a lesion enables the useful analysis and diagnosis of specificity in the lesion (for example, whether the lesion is cancerous).